V. Armand et al., EFFECTS OF VARIOUS VALPROIC ACID-DERIVATIVES ON LOW-CALCIUM SPONTANEOUS EPILEPTIFORM ACTIVITY IN HIPPOCAMPAL SLICES, Epilepsy research, 22(3), 1995, pp. 185-192
Lowering of extracellular calcium induces the development of spontaneo
us epileptiform activities in rat hippocampal slices. The antiepilepto
genic effect of four new sugar-ester derivatives of valproic acid-dime
thylenexylitol valproate, monoacetoneglucose valproate, diacetonegluco
se valproate and glucose valproate-were investigated on such activity
through 20-min bath applications and their effect compared to that of
valproate, valpromide and phenytoin. Sodium valproate, 5 mM, did not c
ompletely suppress the spontaneous epileptiform activity. Valpromide,
2.5 mM, and phenytoin, 0.25 mM, produced complete cessation of seizure
activity. Dimethylenexylitol valproate, 0.1 mM, completely suppressed
spontaneous epileptiform activities. The other derivatives were less
potent: concentrations of 0.25 mM of monoacetoneglucose valproate and
1 mM of diacetoneglucose valproate and glucose valproate were required
for complete cessation of activity. The sugar carriers alone were dev
oid of effect. The data show that these molecules have a direct action
on the nervous tissue and their antiepileptogenic efficacy in the low
-calcium model is far larger than that of valproic acid itself. Such d
erivatives, especially dimethylenexylitol valproate, appear to be prom
ising for development of new antiepileptic molecules.